The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article
Abstract
Considering the urgency of the ongoing COVID-19 pandemic, detection of various new mutant strains and future potential re-emergence of novel coronaviruses, repurposing of approved drugs such as Ivermectin could be worthy of attention. This evidence-based review article aims to discuss the mechanism of action of ivermectin against SARS-CoV-2 and summarizing the available literature over the years. A schematic of the key cellular and biomolecular interactions between Ivermectin, host cell, and SARS-CoV-2 in COVID-19 pathogenesis and prevention of complications have been proposed.The role of Ivermectin against the SARS-CoV-2 virus
The targets of activity of Ivermectin can be divided into the following four groups:- A.
Direct action on SARS-CoV-2
Level 1: Action on SARS-CoV-2 cell entry
Level 2: Action on Importin (IMP) superfamily
Level 3: Action as an Ionophore - B.
Action on host targets important for viral replication
Level 4: Action as an antiviral
Level 5: Action on viral replication and assembly
Level 6: Action on post-translational processing of viral polyproteins
Level 7: Action on Karyopherin (KPNA/KPNB) receptors - C.
Action on host targets important for inflammation
Level 8: Action on Interferon (INF) levels
Level 9: Action on Toll- like-Receptors (TLRs)
Level 10: Action on Nuclear Factor-κB (NF-κB) pathway
Level 11: Action on the JAK-STAT pathway, PAI-1 and COVID-19 sequalae
Level 12: Action on P21 activated Kinase 1 (PAK-1)
Level 13: Action on Interleukin-6 (IL-6) levels
Level 14: Action on allosteric modulation of P2X4 receptor
Level 15: Action on high mobility group box 1 (HMGB1),
Level 16: Action as an immunomodulator on Lung tissue and olfaction
Level 17: Action as an anti-inflammatory - D.
Action on other host targets
Level 18: Action on Plasmin and Annexin A2
Level 19: Action on CD147 on the RBC
Level 20: Action on mitochondrial ATP under hypoxia on cardiac function